Monoethylcholine as a false transmitter precursor at the frog and mouse neuromuscular junctions

Abstract

Monoethylcholine (MECH) enters motor nerve terminals where it is made into acetylmonoethylcholine (AMECH). AMECH opens endplate channels for about half of the average duration observed where they are opened by acetylcholine (ACH). Therefore when AMECH is present in a quantum the endplate currents decay more rapidly. MECH has been used to measure quantal turnover in motor nerve terminals. We find that the incorporation of AMECH into quanta is blocked by vesamicol, an inhibitor of ACH transport into synaptic vesicles. AMECH is incorporated more rapidly when acetylcholinesterase is inhibited, when the choline uptake inhibitor, hemicholinium-3, is present or when extracellular Na+ (required for active CH uptake) is replaced with methylamine. This suggests that in the absence of these inhibitors CH obtained from released ACH is recycled. Therefore, experiments on the rate of incorporation of MECH are misleading unless CH recycling is prevented. Previous work also suggested that MECH is incorporated at a faster rate into those quanta which are released by stimulation than into those released spontaneously. We conclude that quanta released spontaneously and following nerve stimulation probably come from the same pool. The distribution of t1/2's during the incorporation of MECH can be accounted for in the framework of recent studies of the recycling of synaptic vesicles. We conclude that false transmitter is a valuable tool for studying the loading of quanta, but that there are several complications to be considered when trying to use it to measure the turnover of the population of quanta.